1943 mutations of bacteria from virus sensitivity to … · 318 microbiology: a centenary...

318 Microbiology: A Centenary Perspective

1943 Mutations of Bacteria from Virus Sensitivity toVirus ResistanceS. E. LURIA AND M. DELBRÜCK

After the introduction of pure culture techniques for the study of bac-teria in the late 19th century, it became accepted that bacteria, likehigher organisms, have inherited qualities. A single bacterium iso-

lated on the surface of agar produces a clone of descendants, all of whichresemble the original parent in virtually every respect. However, it alsobecame clear that variants appear in otherwise pure cultures and that thesevariants breed true. What was the origin of such variants?

Despite the widespread recognition of the role of chance mutations inthe genetic variation of higher organisms, bacteriologists were reluctant toextend this concept to bacteria. Bacterial cultures appeared to be plastic.Exposed to adverse environments, cultures quickly gave rise to geneticallystable types adapted to the new conditions. The majority of bacteriologists inthe early 20th century believed that environment directly induced some orall of the cells in the population to become stably adapted. Obviously themuch faster rate of growth of bacteria than of higher organisms contributedto the appearance of plasticity. Various mechanisms other than mutationwere proposed for these variations, including shifts in chemical equilibria byHinshelwood (A. C. R. Dean and C. Hinshelwood, p. 21–45, in E. F. Daviesand R. Davies [ed.], Adaptation in Microorganisms, Cambridge UniversityPress, Cambridge, U.K., 1953). The absence of sexual differentiation and of achromosome visible by light microscopy made it easier to accept a differentmode of inheritance for bacteria. The phenomenon of induced enzymebiosynthesis, which had not been clarified at that time, lent circumstantialweight to the plasticity view.

Against this background, the first clear-cut evidence for the occurrenceof spontaneous mutation in bacteria was provided by Luria and Delbrück in1943. They demonstrated that, when a sensitive culture is plated in the pres-ence of an excess of bacteriophage T1, colonies arise from phage-resistantmutants, which were present in the inoculum before exposure to the phage.Luria and Delbrück used fluctuations in the fraction of resistant mutantsacross a series of cultures to argue that the phage-resistant mutants predat-ed selection by the phage. The Luria-Delbrück paper took a solid first steptoward showing that bacteria had genes like plants and animals.

Luria and Delbrück were an effective team. They had agreed to studythe problem of “secondary growth” (of the phage-resistant mutants) in Aprilof 1941. However, the problem proved harder than expected. Early attemptsto devise critical experiments were unsuccessful during Luria’s visit toDelbrück at Vanderbilt University in the fall term of 1942. However, Luriacontinued working on the problem at Indiana University, where he was anAssistant Professor. Luria, in Delbruck’s words, “. . . early in 1943 hit on asatisfactory method of deciding the issue. This method was worked out, thetheory by me here at Vanderbilt, the experimental technique by Dr. Luria atIndiana.” Delbruck and Luria then went on to create a whole new school ofphage genetic research.

A. DALE KAISER

Reprinted from Genetics 28:491–511. Copyright © 1943 by Genetics Society ofAmerica.

Molecular Biology and Physiology 319

320 Microbiology: A Centenary Perspective

Molecular Biology and Physiology 321

322 Microbiology: A Centenary Perspective

Molecular Biology and Physiology 323

324 Microbiology: A Centenary Perspective

Molecular Biology and Physiology 325

326 Microbiology: A Centenary Perspective

Molecular Biology and Physiology 327

328 Microbiology: A Centenary Perspective

Molecular Biology and Physiology 329

330 Microbiology: A Centenary Perspective

Molecular Biology and Physiology 331

332 Microbiology: A Centenary Perspective

Molecular Biology and Physiology 333

334 Microbiology: A Centenary Perspective

Molecular Biology and Physiology 335

336 Microbiology: A Centenary Perspective

Molecular Biology and Physiology 337

338 Microbiology: A Centenary Perspective

Molecular Biology and Physiology 339